The concept of vulnerable plaque is well established with increasing evidence from clinical and basic research. The paradigm has shifted from focusing exclusively on the hemodynamic effects of plaque (ie, resulting lumenal stenosis alone as a predictor of stroke risk) to assessment of the structure and composition of plaque (eg, denuded endothelium with inflammatory elements as a nidus for platelet-fibrin clumping). It is increasingly evident that methods to detect and characterize vulnerable plaque must be developed and optimized. Although MR imaging, CT, and ultrasound provide data regarding single lesions, future investigations relying heavily on nuclear medicine techniques may offer functional assessment of the entire cardiovascular system.